Longitudinal brain structural alterations in patients with nasopharyngeal carcinoma early after radiotherapy

BACKGROUND AND PURPOSE: To investigate effects of radiotherapy on normal brain tissue using in vivo neuroimaging in patients with nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: We used longitudinal MRI to monitor structural brain changes during standard radiotherapy in patients newly diagnosed with NPC. We assessed volumetric measures in 63 patients at 2–3 time points before and after radiotherapy, with 20 NPC-free participants as normal controls. Images were processed using validated software (FreeSurfer). Automated results were inspected visually for accuracy. We examined changes in volume of the whole brain, gray matter, white matter, and ventricles, as well as in cerebral volumes partitioned into temporal, frontal, parietal, and occipital lobes. A linear mixed model was used to evaluate longitudinal changes in these measurements. Statistical significance was evaluated at p < 0.05, which was corrected for multiple comparisons. RESULTS: Volumes of the gray matter, and bilateral temporal lobes decreased in a time-dependent manner, whereas ventricle volume showed a time-dependent increase after radiotherapy. No volume changes were detected in NPC patients before radiotherapy when compared normal controls. No volume changes were detected in the subcohort of patients after completion of induction chemotherapy but prior to initiation of radiotherapy. Changes of bilateral temporal lobe volume correlated with irradiation dose in this region. Expansion of the ventricles correlated with a reduction in cognition assessment. CONCLUSIONS: We detected significant and progressive radiotherapy-associated structural changes in the brains of patients with NPC who were treated with standard radiotherapy, especially in the bilateral temporal lobe in which the effect was dose-dependent. Expansion of the ventricles can serve as an imaging marker for treatment-related reduction in cognitive function. Future studies with longer follow-ups are needed to evaluate morphometric changes long-term after radiotherapy.